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Scientific Reports Jun 2024Acetaminophen (APAP) is a leading cause of acute liver failure. The effect of APAP metabolite's effects in the periphery are well characterized; however, associated...
Acetaminophen (APAP) is a leading cause of acute liver failure. The effect of APAP metabolite's effects in the periphery are well characterized; however, associated consequences in the brain remain poorly understood. Animal studies on this subject are few and reveal that frequent APAP intake can trigger cerebral abnormalities that vary depending on the subject's age. Alarmingly, experimental efforts have yet to examine associated consequences in elderly hosts, who correspond to the highest risk of medication overload, impaired drug clearance, and cognitive deficits. Here, we interrogated the cerebral and peripheral pathology of elderly mice submitted to monthly episodes of APAP intoxication since a young adult age. We found that weeks after the final episode of recurrent APAP exposure, mice exhibited worsened non-spatial memory deficit whereas spatial memory performance was unaltered. Interestingly, one month after the period of APAP intoxication, these mice showed increased glial burden without associated drivers, namely, blood-brain barrier disruption, cholesterol accumulation, and elevation of inflammatory molecules in the brain and/or periphery. Our experimental study reveals how recurrent APAP exposure affects the cognitive performance and cellular events in elderly brains. These data suggest that APAP-containing pharmacological interventions may foreshadow the elevated risk of neuropsychiatric disorders that afflict elderly populations.
Topics: Animals; Acetaminophen; Cognitive Dysfunction; Mice; Astrocytes; Microglia; Male; Brain; Mice, Inbred C57BL; Blood-Brain Barrier; Aging; Disease Models, Animal; Spatial Memory
PubMed: 38902507
DOI: 10.1038/s41598-024-65185-z -
Mikrochimica Acta Jun 2024The introduced work represents an implementation of the automatic benchtop electrochemical station (BES) as an effective tool for the possibilities of high-throughput...
The introduced work represents an implementation of the automatic benchtop electrochemical station (BES) as an effective tool for the possibilities of high-throughput preparation of modified sensor/biosensors, speeding up the development of the analytical method, and automation of the analytical procedure for the determination of paracetamol (PAR) and dopamine (DOP) as target analytes. Within the preparation of gold nanoparticles modified screen-printed carbon electrode (AuNPs-SPCE) by electrodeposition, the deposition potential E, the deposition time t, and the concentration of HAuCl were optimized and their influence was monitored on 1 mM [Ru(NH)] redox probe and 50 μM DOP. The morphology of the AuNPs-SPCE prepared at various modification conditions was observed by SEM. The analytical performance of the AuNPs-SPCE prepared at different modification conditions was evaluated by a construction of the calibration curves of DOP and PAR. SPCE and AuNPs-SPCE at modification condition providing the best sensitivity to PAR and DOP, were successfully used to determine PAR and DOP in tap water by "spike-recovery" approach. The BES yields better reproducibility of the preparation of AuNPs-SPCE (RSD = 3.0%) in comparison with the case when AuNPs-SPCE was prepared manually by highly skilled laboratory operator (RSD = 7.0%).
Topics: Acetaminophen; Dopamine; Gold; Metal Nanoparticles; Electrochemical Techniques; Electrodes; Biosensing Techniques; Limit of Detection; Carbon
PubMed: 38898321
DOI: 10.1007/s00604-024-06454-6 -
Scientific Reports Jun 2024The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight... (Meta-Analysis)
Meta-Analysis
The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence.Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433 ).
Topics: Humans; Abortion, Habitual; Heparin, Low-Molecular-Weight; Female; Pregnancy; Aspirin; Anticoagulants; Randomized Controlled Trials as Topic; Live Birth
PubMed: 38898143
DOI: 10.1038/s41598-024-62949-5 -
Molecules (Basel, Switzerland) May 2024Volatile oil serves as a traditional antipyretic component of Bupleuri Radix. var. (Wolff) Shan et Y. Li belongs to the genus and is distinguished for its high level...
Volatile oil serves as a traditional antipyretic component of Bupleuri Radix. var. (Wolff) Shan et Y. Li belongs to the genus and is distinguished for its high level of saikosaponins and volatile oils; nonetheless, prevailing evidence remains inconclusive regarding its viability as an alternative resource of other official species. This study aims to systematically compare the volatile oil components of both dried and fresh roots of var. and the four legally available species across their chemical, molecular, bionics, and anatomical structures. A total of 962 compounds were determined via GC-MS from the dried roots; var. showed the greatest differences from other species in terms of hydrocarbons, esters, and ketones, which was consistent with the results of fresh roots and the e-nose analysis. A large number of DEGs were identified from the key enzyme family of the monoterpene synthesis pathway in var. via transcriptome analysis. The microscopic observation results, using different staining methods, further showed the distinctive high proportion of phloem in var. , the structure which produces volatile oils. Together, these pieces of evidence hold substantial significance in guiding the judicious development and utilization of genus resources.
Topics: Oils, Volatile; Bupleurum; Plant Roots; Gas Chromatography-Mass Spectrometry; Plants, Medicinal
PubMed: 38893436
DOI: 10.3390/molecules29112561 -
International Journal of Molecular... Jun 2024Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment...
Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment among individuals without prior liver ailments. The primary reasons for liver failure are infection with hepatitis virus or overdose of certain medicines, such as acetaminophen. (PT), a type of microalgae known as a diatom species, has been reported to contain an active ingredient with anti-inflammatory and anti-obesity effects. In this study, we evaluated the preventive and therapeutic activities of PT extract in acute liver failure. To achieve our purpose, we used two different acute liver failure models: acetaminophen- and D-GalN/LPS-induced acute liver failure. PT extract showed protective activity against acetaminophen-induced acute liver failure through attenuation of the inflammatory response. However, we failed to demonstrate the protective effects of PT against acute liver injury in the D-GalN/LPS model. Although the PT extract did not show protective activity against two different acute liver failure animal models, this study clearly demonstrates the importance of considering the differences among animal models when selecting an acute liver failure model for evaluation.
Topics: Animals; Acetaminophen; Mice; Chemical and Drug Induced Liver Injury; Microalgae; Disease Models, Animal; Liver Failure, Acute; Male; Protective Agents; Ethanol; Diatoms; Liver; Lipopolysaccharides
PubMed: 38892435
DOI: 10.3390/ijms25116247 -
International Journal of Molecular... May 2024Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis...
Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24-72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUV) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUV compared to controls ( = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET's potential as a non-invasive imaging biomarker for early-stage ALF.
Topics: Animals; Liver Failure, Acute; Acetaminophen; Male; Mice; Mice, Inbred C57BL; Receptors, GABA; Positron-Emission Tomography; Liver; Positron Emission Tomography Computed Tomography; Fluorine Radioisotopes; Radiopharmaceuticals; Disease Models, Animal; Carbazoles
PubMed: 38892130
DOI: 10.3390/ijms25115942 -
Cell Communication and Signaling : CCS Jun 2024Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the...
A novel approach to alleviate acetaminophen-induced hepatotoxicity with hybrid balloon flower root-derived exosome-like nanoparticles (BDEs) with silymarin via inhibition of hepatocyte MAPK pathway and apoptosis.
INTRODUCTION
Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the therapeutic effects of drug-induced hepatotoxicity of BDEs have not been elucidated. BDEs contain a large amount of platycodin D, which is widely known to be effective in regulating inflammation and ameliorating systemic toxicity. Thus, the main therapeutic activity of BDEs is attributed to inhibiting the inflammatory response and alleviating toxicity. In this study, we fabricated the hybrid BDEs fused with liposomes containing silymarin (SM) to enhance the synergistic effect on inhibition of acetaminophen-induced hepatotoxicity (APAP).
OBJECTIVE
Considering the potential therapeutic effects of BDEs, and the potential to achieve synergistic effects to improve therapeutic outcomes, we constructed hybrid BDEs with a soy lecithin-based liposome loaded with SM. Since liposomes can provide higher thermal stability and have greater structural integrity, these might be more resistant to clearance and enzymatic degradation of drug molecules.
METHODS
Hybrid BDEs with liposome-loaded SM (BDEs@lipo-SM) were fabricated by thin-film hydration and extrusion. BDEs@lipo-SM were characterized using dynamic light scattering and high-performance liquid chromatography. After confirmation of the physical properties of BDEs@lipo-SM, various therapeutic properties were evaluated.
RESULTS
BDEs@lipo-SM were internalized by hepatocytes and immune cells and significantly decreased mRNA expression of apoptosis and inflammation-relevant cytokines by inhibiting the hepatocyte MAPK pathway. BDEs@lipo-SM significantly induced an increase in glutathione levels and inhibited APAP-induced hepatotoxicity.
CONCLUSION
From this study, we know that BDEs are reliable and safe nanovesicles containing natural metabolites derived from balloon flower, and they can facilitate intercellular communication. BDEs are also easily modified to enhance drug loading capacity, targeting effects, and long-term accumulation in vivo. BDEs@lipo-SM have therapeutic benefits for acute liver injury and can alleviate cell death and toxicity. They can be efficiently delivered to the liver and effectively inhibit APAP-induced hepatotoxicity by inhibiting the MAPK signaling pathway and apoptosis, which accelerates liver recovery in the APAP-induced acute liver injury model. These findings highlight that BDEs represent an attractive delivery vehicle for drug delivery.
Topics: Acetaminophen; Apoptosis; Animals; Nanoparticles; Exosomes; Hepatocytes; Silymarin; MAP Kinase Signaling System; Mice; Chemical and Drug Induced Liver Injury; Humans; Liposomes; Male; Plant Roots; Mice, Inbred C57BL
PubMed: 38890646
DOI: 10.1186/s12964-024-01700-z -
Scandinavian Journal of Pain Jan 2024Chronic pain is highly prevalent in nursing home residents and often occurs with depression as well as cognitive impairment, which can severely influence and limit the...
OBJECTIVES
Chronic pain is highly prevalent in nursing home residents and often occurs with depression as well as cognitive impairment, which can severely influence and limit the expression of pain.
METHODS
The present cross-sectional study aimed to estimate the prevalence of pain, depressive mood, and cognitive impairment in association with pharmacological treatment against pain and depressive symptoms among Swedish nursing home residents.
RESULTS
We found an overall pain prevalence of 52.8%, a prevalence of 63.1% for being in a depressive mood, and a prevalence of cognitive impairment of 68.3%. Among individuals assessed to have depressive mood, 60.5% were also assessed to have pain. The prevalence of pharmacological treatment for pain was 77.5 and 54.1% for antidepressants. Prescription of pharmacological treatment against pain was associated with reports of currently having pain, and paracetamol was the most prescribed drug. A higher cognitive function was associated with more filled prescriptions of drugs for neuropathic pain, paracetamol, and nonsteroidal anti-inflammatory drugs (NSAIDs), which could indicate an undertreatment of pain in those cognitively impaired.
CONCLUSION
It is important to further explore the relationship between pain, depressive mood, and cognitive impairment in regard to pain management in nursing home residents.
Topics: Humans; Nursing Homes; Sweden; Male; Female; Cross-Sectional Studies; Prevalence; Depression; Aged, 80 and over; Aged; Cognitive Dysfunction; Pain Management; Antidepressive Agents; Chronic Pain; Acetaminophen; Analgesics
PubMed: 38887790
DOI: 10.1515/sjpain-2024-0007 -
Cureus May 2024Chenopodium ambrosioides L. is a plant belonging to the Chenopodiaceae family, known for its use in traditional medicine as a remedy for its antiseptic, analgesic,...
Chenopodium ambrosioides L. is a plant belonging to the Chenopodiaceae family, known for its use in traditional medicine as a remedy for its antiseptic, analgesic, antipyretic, antispasmodic, and anti-inflammatory properties. It is used for its therapeutic properties internally as an infusion or externally as a vermifuge. Its use can be responsible for serious, even fatal, side effects and intoxications, particularly in infants and children. These may include neurological, digestive, hepatic, or renal complications. We present a case of Chenopodium ambrosioides L. intoxication in a four-year-old girl, resulting from repeated high-dose infusions of this plant for antipyretic purposes. She was admitted to the pediatric emergency department for management of a disorder of consciousness four hours after ingesting Chenopodium ambrosioides L. to treat acute fever.
PubMed: 38883026
DOI: 10.7759/cureus.60351 -
Journal of Pharmacy & Bioallied Sciences Apr 2024also known as the "King of Bitters" is a herbal medicine of the family which is native to India and Sri Lanka. is a very useful medicinal plant as it has antioxidant,...
also known as the "King of Bitters" is a herbal medicine of the family which is native to India and Sri Lanka. is a very useful medicinal plant as it has antioxidant, antidiabetic, antipyretic, anticancer properties. The main antibacterial activity of is due to the presence of andrographolide and arabinogalactan proteins. The medicinal properties of rose are mostly due to their abundance in phenolic compounds. They have many pharmacological properties like antibacterial, antioxidant, thrombolytic, and anticancer properties. The hips of the rose plant have Vitamin C in a concentration that is three times more than a citrus fruit that can be used in the treatment of a flu or a cold. Mueller-Hinton agar was utilized for this activity to determine the zone of inhibition. The plant extracts with different concentrations were loaded, and the plates were incubated for 24 hours at 37°C. After the incubation time, the zone of inhibition was measured. The results of this study are significant because they demonstrate the antibacterial activity of against three bacterial pathogens. This suggests that the formulation of has potential as a natural antibacterial agent. Further studies are needed to explore the mechanism of action and potential applications of this formulation. In conclusion, the study shows that the formulation of has significant antibacterial activity against , , . This suggests that the formulation of has potential as a natural antibacterial agent that could be further explored for its potential use in the treatment of bacterial infections.
PubMed: 38882789
DOI: 10.4103/jpbs.jpbs_574_23